1. Field of the Invention
This invention relates to the quality assurance testing of instruments which read electrical signals from electrochemical sensor arrays carried on insertable sensor devices, and in particular, to a reusable test unit for use with portable battery-powered blood analyzers.
2. Description of the Problems Addressed
Portable analyzer systems, such as that disclosed in co-pending U.S. patent application Ser. No. 07/245,102 filed Sept. 15, 1988, provide challenges for quality assurance which have not been addressed in the prior art. Some of these challenges arise from the clinical setting in which the analyzer is used, and some arise from the technology employed in the system.
In a clinical setting, it has long been acknowledged that a relatively wide variation in measured values can result when identical samples are sent to different laboratories, even if each laboratory, considered individually, provides repeatable results and good internal precision. As a practical matter, variation across laboratories need not be of clinical concern for patient monitoring, if samples from a given patient are always sent to the same laboratory for testing on the same instrument. However, the convenience of a portable analyzer, and the likelihood that many such instruments may be available for use in the emergency room, in the intensive care unit, and elsewhere in the hospital or doctor's office, raise the possibility that tests on consecutive samples from the same patient may be performed with different analyzers. In that case, an unknown bias in a particular portable analyzer could be misinterpreted as a change in the patient's condition, or could mask such a change.
The diagnostic value of measurements from a portable instrument, and the reliance which a physician can place on such measurements, would be enhanced by the provision of a test unit for periodic functional testing of all the portable instruments at a particular location, to ensure that each is functioning properly and that their measurements would be in agreement within an established tolerance.
The nature of the technology employed in a portable system with disposable sensor devices can considerably compound the difficulty of providing a suitable test unit. At the outset, it should be noted that a need for frequent yet convenient and economical testing of the instrument is to be expected. If questionable results are obtained, the user needs a way to distinguish between a failure of the instrument and a defective or contaminated batch of disposable sensor devices. However, the specific implementations of the system elements, including sensors, electronic components, and connectors, each provide additional difficulties.
In particular, microfabricated electrochemical sensors (for example, those disclosed in co-pending U.S. patent application Ser. No. 07/432,714 filed Nov. 7, 1989) may be advantageous for use in disposable sensor devices, but their extremely small size leads to very weak, interference-sensitive, high-impedance signals. These signals must be amplified under demanding conditions, presenting a highly passive input to the sensor, which neither draws much current from the sensor nor permits that current to vary as the electrochemical potential from the sensor varies.
Since the portable instrument is battery powered, the amplifiers must present low power requirements. CMOS operational amplifiers are best suited to that role, but are highly susceptible to damage or performance degradation from static discharges. Consequently, an amplifier which initially provides the required input characteristics may no longer operate within specifications after continued exposure to static in normal use, and a provision for testing the integrity of the amplifiers is highly desirable.
While traditional laboratory analyzer systems present only the fluidic inputs to the user environment, the portable analyzer and disposable sensing device also expose electrical contacts. It can be expected that a clinical environment will provide frequent opportunities for contamination of contacts, through accident, misuse, or prolonged exposure to the environment in normal use. The difficulties which can arise are heightened by the small scale of the system. Input pins for the sensors are extremely close together, increasing the chances of contamination across adjacent pins leading to cross-talk between the high-impedance sensor signals.
As an aid to explanation, a typical portable instrument system is shown schematically in FIG. 1. At the left, item 110 represents an array of microfabricated sensors on a disposable sensor device. (For simplicity, only three sensors are provided in this example.) A connector 120 forms the electrical connections between the sensors and a portable instrument. Within the instrument, front end CMOS operational amplifiers 130, 140, and 150 provide low-impedance, relatively noise insensitive signals faithful to the signals from the sensors, for further processing by the instrument in circuitry (not shown) to the right of switches 160, 170, and 180. Dashed line 190 divides the Figure into two domains, and represents the interface between them. To the left is a high-impedance electrochemical domain, while to the right is a low-impedance electronic domain.
The considerations discussed above lead to a need to test on both sides of the interface indicated by line 190, including connector 120. Indeed, experience indicates that problems are more likely to occur on the sensitive electrochemical side than on the relatively more predictable electronic side.
Ideally, a test unit to solve these problems would be capable of testing elements on both sides of the interface, providing simulated high-impedance sensor signals to be passed through the connector. In addition, such a test unit would be reusable to reduce costs and be simple to operate to avoid operator error. It is also desirable that it not require the use or replacement of costly chemicals, and that it be robust to survive exposure to the clinical environment without degradation of performance. Furthermore, an optimal test unit would permit different failure modes to be readily distinguished.
3. Discussion of the Prior Art
Generally, traditional testing schemes do not directly address the problems outlined in the discussion above. For example, the software in many microprocessor-based electronic instruments includes a self-test routine which is performed at power-up or may be invoked by a user. While such a self-test routine may advantageously be employed in a portable analyzer to check many functions of the instrument, such internal testing cannot test the interface with the high-impedance electrochemical domain. To verify the performance of an instrument which measures an external physical parameter, and to test the performance of the interface through which signals are received, it is necessary to inject an externally established test signal through the interface.
Likewise, the necessary testing cannot be accomplished through common batch calibration techniques. Typically, batch calibration is accomplished by shipping a calibrator with each batch of sensors or reagents, which reflects the characteristics of that particular batch. It serves to correct the internal calibration curve used by the analyzer as appropriate for that specific batch, but it does not test the analyzer function.
One attempt to provide signal simulation for an instrument is related to U.S. Pat. No. 4,756,884 to Hillman et al. and involves capillary flow devices for optical measurement of prothrombin or clotting time. In the measurement system, sold by Biotrack, Inc. of Sunnyvale, Calif., a disposable sample card is provided with chambers through which a blood sample will flow; the sample card is inserted into an instrument which detects a change in optical density resulting from clotting. Testing is accomplished with a reusable "monitor control cartridge" (supplied with the instrument) which may be inserted in the same manner as a sample card. When a button on the monitor cartridge is pressed, an electrochromic element in the cartridge simulates the optical behavior of a blood sample, to verify that the instrument is functioning.
The monitor cartridge, however, simulates only a single optical signal. It does not emulate the high-impedance signals of electrochemical sensors, and does not test the integrity of electrical connectors or amplifiers.
Another testing technique is provided by the ChemPro system, corresponding to that disclosed in U.S. Pat. No. 4,654,127 to Baker et. al. The ChemPro analyzer provides prompts to the user to perform various steps in the measurement process. Prior to signalling the user to insert a sample card, the instrument switches on the amperometric channel normally used for glucose measurements. If an open circuit is detected, the analyzer is assumed to be functional and the user is prompted to insert the sample card. If the instrument does not detect an open circuit, the unit will not provide test instructions to the user, but instead will display instructions to insert a connector cleaning card.
That approach has only limited utility in testing the instrument-sample card interface. For example, there is no provision to test for leakage currents in all of the connector pins, a deficiency which is particularly noticed for those circuits most susceptible, namely, the potentiometric circuits. Also, testing only for an open circuit on the amperometric channel is inadequate to determine if the measurements will be accurate.
Another testing scheme for conventional analyzers is represented by the VWR brand Mini-Test Electrode Simulator. This battery powered device is intended to simulate the characteristics of a pH electrode, for testing pH meters. Switches are provided to select the pH level to be emulated, and cables are provided with connectors compatible with standard pH meters.
That electrode simulator, however, does not simulate the electrochemical characteristics of microfabricated sensor arrays, nor does it serve to test closely spaced connector pins. It also has no provision for emulating the many different sensors, which may be amperometric, potentiometric, or conductimetric, which may be simultaneously used on a single disposable sensor device.